“Diazepam is effective, but some drawbacks include the way it must be administered (either by IV or rectal suppository), and it may not work depending on how long the seizure goes,” lead author Dr. Jason McMullan told Reuters Health.
“Midazolam can be effective in other non IV routes — an intramuscular injection, a spray into the nose, or buccally — and those routes may be better, especially for home use and for paramedics to treat someone before they make it to the hospital,” he added.
In their systematic literature review, Dr. McMullan, an emergency department physician at the University of Cincinnati, Ohio, and his associates identified six randomized controlled trials that met CONSORT-based quality measures comparing midazolam and diazepam for treatment of status epilepticus. The trials included 774 subjects. One trial involved patients up to 22 years old; the other five included only children.
Dosing for diazepam was 0.2-0.3 mg/kg IV or 0.5 mg/kg rectally. Intramuscular and intranasal midazolam was dosed at 0.2 mg/kg, or 0.5 mg/kg via the buccal route. One study used 10-mg fixed doses of rectal diazepam and buccal midazolam.
Overall, midazolam was superior to diazepam in seizure cessation. There were 170 episodes of failure to achieve seizure cessation with diazepam versus 112 with midazolam (relative risk 1.52, number needed to treat = 7).
In three studies comparing rectal diazepam to buccal midazolam, the latter was more successful in achieving seizure cessation. There was no significant difference between non-IV midazolam compared with IV diazepam.
However, non-IV midazolam was administered a mean of 2.46 minutes more quickly than IV diazepam. And in treating status epilepticus, minutes can make a big difference, Dr. McMullan said.
“The longer someone seizes, the worse they do, and they’ll often require higher doses to make it stop, which can have untoward side effects,” he explained.
Both agents were safe, with only three complications requiring intervention in the diazepam group and two in the midazolam group.
Many cities already have protocols in place for using midazolam in EMS systems, which Dr. McMullan recommends. “Unfortunately there’s not a commercially available product for midazolam for prescription, but it is something that should be explored for at-home use,” he added.
“And it is certainly an option for emergency department use, if the patient needs immediate treatment and does not already have an IV established.”
Dr. McMullan pointed out that they found no evidence for the use of midazolam in adults, or any comparison with lorazepam (Ativan), the “generally accepted standard in emergency departments.” The authors propose prospective clinical trials to confirm the efficacy and safety of non-IV midazolam for treatment of status epilepticus.
Acad Emerg Med 2010;17:575-582.